1 New and emerging non-invasive glucose monitoring technologies Horizon Scanning Research & Intelligence Centre May 2016
Welcome message from author
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
1
New and emerging non-invasive glucose monitoring technologies
Horizon Scanning Research & Intelligence Centre
May 2016
2
The National Institute for Health Research Horizon Scanning Research & Intelligence Centre (NIHR HSRIC) is based at the University of Birmingham in the UK. The NIHR HSRIC aims to supply timely information to key health policy and decision-makers and research funders within the NHS about emerging health technologies that may have a significant impact on patients or the provision of health services in the near future. The scope of our activity includes pharmaceuticals, medical devices and equipment, diagnostic tests and procedures, therapeutic interventions, rehabilitation and therapy, and public health activities.
HSRIC reports can be accessed via our website at: www.hsric.nihr.ac.uk, and the centre can be followed on Twitter at: @OfficialNHSC.
This report presents independent research funded by the National Institute for Health Research (NIHR). The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.
The NIHR Horizon Scanning Research & Intelligence Centre,
University of Birmingham, United Kingdom [email protected]
www.hsric.nihr.ac.uk
Copyright © University of Birmingham 2016
3
CONTENTS
EXECUTIVE SUMMARY ................................................................................................................................. 4
ACKNOWLEDGEMENTS ............................................................................................................................... 5
1 INTRODUCTION ………………………………………………………………………………………………………………………………… 6
1.1 DIABETES ........................................................................................................................................... 6
1.2 MANAGEMENT OF DIABETES ............................................................................................................ 7
1.3 BLOOD GLUCOSE MONITORING ........................................................................................................ 8
1.4 ALTERNATIVE GLUCOSE MONITORING TECHNOLOGIES ................................................................... 8
2 AIMS …………………………………………………………………………………………………………………………………………………..9
3 METHODS ............................................................................................................................................... 10
3.1 TECHNOLOGY IDENTIFICATION ....................................................................................................... 10
3.2 FILTRATION ...................................................................................................................................... 10
3.3 HEALTHCARE PROFESSIONALS’ PERSPECTIVE ................................................................................. 10
3.4 PATIENT AND CARER PERSPECTIVE ................................................................................................. 11
4 RESULTS .................................................................................................................................................. 12
4.1 IDENTIFICATION AND FILTRATION OF RESULTS .............................................................................. 12
4.2 TYPES OF NIGM TECHNOLOGIES ..................................................................................................... 14
4.3 NIGM TECHNIQUES ......................................................................................................................... 14
4.4 DEVELOPMENT STATUS ................................................................................................................... 17
4.5 HEALTHCARE PROFESSIONALS’ PERSPECTIVE ................................................................................. 18
4.6 PEOPLE WITH DIABETES AND CARERS PERSPECTIVE ...................................................................... 19
5 DISCUSSION ............................................................................................................................................ 21
APPENDICES ............................................................................................................................................... 23
Appendix 1. Identification sources and search terms ....................................................................... 23
Appendix 2. List of developers identified .......................................................................................... 25
Appendix 3. Technical questionnaire sent to developers ................................................................. 26
Appendix 4: New and emerging NIGM technologies identified ........................................................ 27
Appendix 5: Pictures of NIGM technologies ...................................................................................... 54
REFERENCES .............................................................................................................................................. 56
4
EXECUTIVE SUMMARY
Diabetes is a common life-long condition where the levels of glucose in the body are too high because the body is unable to convert it to energy due to insufficient insulin or the insulin not working properly. There are two main types of diabetes, type 1 and type 2. These are managed on a daily basis by regular self-testing and depending on the type, insulin therapy, medication and lifestyle changes to maintain appropriate blood glucose levels. Currently people with diabetes monitor their blood glucose by drawing blood via a finger prick then using a hand-held glucose meter. However, this method is generally disliked due to the pain and inconvenience associated with finger pricking. The development of a safe and reliable non-invasive glucose monitor may provide patients with an alternative, painless method. This horizon scanning review aimed to identify new and emerging non-invasive glucose monitoring (NIGM) technologies for people with type 1 and 2 diabetes. We identified relevant technologies by searching online sources of information (such as clinical trials and bibliographic databases, and the medical media) and the NIHR Horizon Scanning Research & Intelligence Centre database of emerging technologies. We then approached developers to obtain further information about the NIGM technologies identified. We also involved healthcare professionals and people with type 1 diabetes and their carers to find out their perspectives on these emerging technologies. A total of 40 NIGM technologies were identified and are presented in this report. Thirty-nine were being tested in clinical research studies and one is available through the developer’s website. Of the 40 NIGM technologies identified, 24 were intermittent NIGMs and 16 were continuous NIGMs. Three general glucose monitoring technique categories were identified: optical, transdermal and electrochemical techniques. Potential sites of testing included skin, tear fluid, saliva and breath. The report also summarises the views expressed by healthcare professionals and people with diabetes and their carers on the technologies identified. These include comments on the benefits they think NIGM technologies might bring, the important features that they would like to see in future commercial technologies, and what the key issues will be concerning their use and adoption into the healthcare system. For many technologies development is still in the early stages so there was limited information regarding safety and effectiveness. People with diabetes and their carers were very interested in the development of NIGM technologies and thought their use could potentially improve their quality of life but had reservations about reliability, safety, appearance and usability.
We would welcome your views on this report. Please take our brief online survey at this link: https://www.surveymonkey.com/s/X7WW6QX
5
ACKNOWLEDGEMENTS
NIHR Horizon Scanning Research & Intelligence Centre review team Angharad Slade Senior Analyst Dr Sue Simpson Reviews team lead Dr Annette Wood Medical Advisor Healthcare professionals The following clinical experts gave us their advice and views on the new and emerging non-invasive glucose monitoring technologies we identified:
Dr Muhammad Ali Karamat, Consultant Physician, Heart of England Foundation Trust, Birmingham and Honorary Senior Lecturer in Diabetes and Endocrinology, University of Birmingham.
Dr Chris Walton, Consultant in Diabetes, Hull and East Yorkshire NHS Hospitals Trust, Hull.
Dr Jackie Elliott, Senior Clinical Lecturer in Diabetes, University of Sheffield, and Honorary Consultant, Sheffield Teaching Hospitals.
Henrietta Mulnier, Lecturer in Diabetes Nursing, King’s College London.
The following expert provided technical advice on the non-invasive glucose monitoring techniques identified within the report:
Dr Sandeep Kumar Vashist, Senior Scientist in Point of Care diagnostics, Royal Melbourne Institute of Technology, Australia.
Members of the public with type 1 and 2 diabetes
Lesley Jordan, Chief Executive, and Melissa Holloway, Chief Adviser, INPUT Patient Advocacy (www.inputdiabetes.org.uk) facilitated the involvement of four members of the public (two people with diabetes and two carers of young people with diabetes) who gave their views on the identified new and emerging non-invasive glucose monitoring technologies. The NIHR Horizon Scanning Research & Intelligence Centre is grateful to all those who helped us to include both a healthcare professionals’ and potential users’ perspective in this report. We thank them for their time and valuable contributions.
6
1. INTRODUCTION
Non-invasive glucose monitoring Currently the self-monitoring of blood glucose requires people with diabetes to draw blood via a finger prick, then use tests strips and a hand-held blood glucose meter to measure their glucose levels1. However, this invasive method is generally disliked due to the pain and inconvenience associated with finger pricking2. The development of a non-invasive glucose monitoring (NIGM) technology may provide people with diabetes with an alternative method. This horizon scanning review provides:
a) An overview of new and emerging NIGM technologies and the potential benefits
of these to people with diabetes who monitor their glucose levels.
b) Information about the individual new and emerging technologies identified by
researchers at the NIHR Horizon Scanning Research and Intelligence Centre
(NIHR HSRIC).
c) Views of healthcare professionals and potential users on the identified NIGM
technologies.
1.1 DIABETES
1.1.1 OVERVIEW
Insulin is a hormone produced by the pancreas that allows glucose to enter the body’s cells. Glucose serves as the primary energy source for most cells in the body and plays an important role in processes such as digestion and cellular respiration3,4. People with diabetes either do not produce enough insulin or the insulin produced does not work properly and as a result, glucose remains in the bloodstream instead of entering the cells3. There are two main types of diabetes, type 1 and type 2. Type 1 diabetes (also known as type 1 diabetes mellitus, insulin dependent diabetes, T1DM and T1D) occurs as a result of the immune system attacking and destroying beta cells in the pancreas that are responsible for producing insulin5. Type 2 diabetes (also known as type 2 diabetes mellitus, insulin resistant diabetes, T2DM and T2D) develops when the beta cells are unable to produce enough insulin or when the insulin produced does not work properly6.
7
1.1.2 PREVALENCE
In 2015, the estimated prevalence of diabetes (both type 1 and 2) in adults between the ages of 20-70 years worldwide was 415 million7. This is expected to increase to 642 million adults by 2040 (one person in 10)7. In the UK, it is estimated that one in 16 people (adults and children) have diabetes (diagnosed or undiagnosed), with approximately four million people living with the condition7. This is estimated to increase to five million by 20257. For all adults and children with diabetes in the UK, it is estimated that 10% have type 1 diabetes and 90% have type 27, which equates to approximately 400,000 and 3.6 million people respectively8. There are around 31,500 children and young people under the age of 19 with diabetes in the UK7. This may be an underestimate as not all children over the age of 15 are managed in paediatric care. Around 95% have type 1 diabetes, 2% have type 2 diabetes and 3% have either maturity onset diabetes of the young (MODY), cystic fibrosis related diabetes or their diagnosis has not been defined7. 1.2 MANAGEMENT OF DIABETES
Effective diabetes management reduces the risk of long-term complications associated with the disease, which include heart disease, blindness, stroke, kidney disease and amputations leading to disability and premature mortality5. The risk of complications is greatly reduced with treatment that maintains the circulating glucose levels to as near as normal as possible, thus reducing tissue damage9. Short term complications can occur if blood glucose levels go too high (hyperglycaemia) or too low (hypoglycaemia). In the latter, blood glucose levels fall to a level that can potentially cause harm and causes symptoms such as sweating, feeling shaky, hunger, tiredness, blurred vision, lack of concentration and headaches10. Severe hypoglycaemia is more serious and requires urgent assistance. It can cause fits, loss of consciousness, coma and even death. In contrast, hyperglycaemia symptoms include an increase in urination (especially at night), headaches, tiredness, lethargy and an increased thirst10. Consistently high blood glucose levels can lead to diabetic ketoacidosis (DKA) where the body uses an alternative energy source to glucose such as fat. This causes a build-up of a potentially harmful by-product called ketones and if left untreated, can lead to diabetic coma or death10,11. For most people with diabetes, managing the condition has an impact on their lifestyle and quality of life. Diabetes is managed on a daily basis by the person with the condition or with the help of a carer. For type 1 diabetes it involves regularly testing blood glucose levels and injecting insulin as and when needed to achieve an appropriate level of glycaemic control and to identify low blood glucose levels before the development of hypoglycaemia12,13. NICE guidelines recommend that adults with type 1 diabetes test their blood glucose levels at least four times a day, including before each meal and before going to bed9. It is recommended that children with type 1 diabetes test their blood at least five times per day14. People with type 2 diabetes do not routinely self-monitor blood glucose levels unless they have insulin dependent type 2 diabetes; evidence of hypoglycaemic episodes; or are on oral medication that may increase their risk of hypoglycaemia while driving or operating machinery15.
8
1.3 BLOOD GLUCOSE MONITORING
Monitoring blood glucose levels helps people with diabetes and their carers make informed decisions about their diet, activity and medication requirements, such as insulin dose. It can also help patients, carers and their healthcare team alter treatments to help prevent long-term complications16. The conventional way for people with diabetes to test their blood glucose levels is through a portable device known as a blood glucose meter. First, the side of a finger is pricked using a lancet to draw a small drop of blood. The blood is then transferred to a test strip which is inserted into the blood glucose meter, which then provides a result. There are currently over 65 blood glucose meters available in the UK varying in size, weight, test time (time to results between 3 and 10 second), memory capabilities and special features17. 1.4 ALTERNATIVE GLUCOSE MONITORING TECHNOLOGIES
1.4.1 CONTINUOUS GLUCOSE MONITORS
Devices that can monitor glucose continuously and automatically are also available, and are known as ‘continuous glucose monitors’ (CGM) or real-time CGM. A typical system includes:
1. a disposable glucose sensor placed just under the skin and worn for a few days until replacement;
2. a link from the sensor to a non-implanted transmitter which communicates to a radio receiver; and
3. an electronic reader/receiver worn like a pager that records and displays glucose levels.
These devices measure the glucose levels in the interstitial fluid (ISF) in and around cells18.
1.4.2 MINIMALLY INVASIVE GLUCOSE MONITORS
Minimally invasive glucose monitoring technologies are so-called because they compromise the skin barrier but don’t puncture any blood vessels19. There has been much research into their development through either decreasing the blood sample volume collected, and/or measuring areas of the body less sensitive than fingertips, such as the forearm, upper arm, or thigh20. However, such systems lack the accuracy and control of currently available systems, especially during the night20. Minimally invasive systems have been developed that sample the ISF, such as the CGMs described earlier. Nonetheless, they suffer from limitations, as the patient still experiences discomfort and most require continuous calibration21.
9
1.4.3 NON-INVASIVE GLUCOSE MONITORS
NIGM technologies monitor glucose levels without compromising the skin barrier. These technologies aim to provide continuous readings similar to the currently used CGMs, or intermittent readings where patient activity is necessary to perform the test.
2 AIMS
The aims of this horizon scanning review were: 1. To identify new and emerging NIGM technologies for people with type 1 and
type 2 diabetes. 2. To determine the stage of development of the identified technologies and where
possible when they might become available for clinical use in the UK (private or NHS).
3. To collect the opinions of experts and people with diabetes and their carers on the potential impact of emerging NIGM technologies.
Inclusion criteria The review sought to identify technologies that were:
New: a technology that is CE marked, has only been available for clinical use for ≤12 months and is generally in the launch or early post-marketing stages.
Emerging: a technology that is expected to be CE marked or launched within the
UK in the next five years.
Non-invasive: technologies that monitor glucose levels without compromising the
skin barrier or involving the introduction of instruments such as needles into the
body.
Used for both intermittent and continuous monitoring of glucose
Indication: Type 1 and 2 diabetes; adults and children. Exclusion criteria We excluded:
Glucose sensing bio-implants
Technologies in very early stage of development (pre-clinical) and technologies that are already widely available in the NHS.
10
3 METHODS
3.1 TECHNOLOGY IDENTIFICATION
We developed a search strategy to identify new and emerging NIGM technologies using the following sources:
Technology databases, including the in-house NIHR HSRIC database,
international horizon scanning databases and commercial databases.
Clinical trial registries.
Bibliographic databases.
Relevant conferences reports and abstracts.
Review articles and commentaries in relevant specialist journals.
Websites and publications of relevant organisations and developers.
These searches were supplemented by searching more general sources of information, such as Google, health media reports and industry news. The search process took place between June and July 2015. A full list of identification sources and search terms used is provided (Appendix 1). 3.2 FILTRATION
A first filtration of identified potential NIGM technologies was carried out by checking the initially available information against our inclusion and exclusion criteria and also removing any obvious duplicates. Next the developers of the remaining technologies identified (Appendix 2) were contacted. A technical questionnaire (Appendix 3) was sent to each developer to request further information to allow a second filtration against the review’s inclusion and exclusion criteria and to enable us to present current and accurate information on each technology. 3.3 HEALTHCARE PROFESSIONALS’ PERSPECTIVE
Seven healthcare professionals who specialise in type 1 and/or type 2 diabetes were invited to comment on the identified technologies. Four agreed and these were:
A consultant Physician and Honorary Senior Lecturer in Diabetes and Endocrinology.
A consultant Physician and Chair of the Association of British Clinical Diabetologists (ABCD).
A Senior Clinical Lecturer in Diabetes and Honorary Consultant.
A lecturer in Diabetes Nursing.
The healthcare professionals were sent tables summarising the identified and filtered technologies and a description of the techniques used and were asked to provide comments on specific aspects of each NIGM technology:
1. Do you believe this technology and the technique used has potential to monitor
glucose levels accurately?
2. What features of the technology, if any, do you believe to be innovative? Are
these innovations significant?
11
3. What is the potential impact of the technology in terms of: patient outcomes
(including quality of life); NHS systems and resources; any other potential
impacts e.g. societal.
4. What potential barriers might there be to this technology coming into routine
NHS use? (e.g. cost, training, service reorganisation)
5. Do you know of any new or emerging non-invasive glucose monitoring
technologies that we have not identified? If so, please let us know about them.
Participants were given three weeks to return their comments. 3.4 PATIENT AND CARER PERSPECTIVE
We collaborated with INPUT Diabetes (http://www.inputdiabetes.org.uk/) to access and enable us to involve people with type 1 and/or 2 diabetes who regularly monitor their blood glucose levels at home. INPUT Diabetes is an organisation that aims to help people access diabetes technology and support from the NHS, including insulin pumps, smart glucose meters and continuous glucose monitoring. A list of technologies identified was sent to the Chief Executive and Chief Adviser of INPUT diabetes and these were circulated via email to two people with diabetes and two carers of children with diabetes. These were:
Female with type 1 diabetes who currently uses finger pricks and a CGM. Also uses an insulin pump.
Female with type 1 diabetes who currently uses interstitial and finger prick glucose monitoring
Carer of a young boy who currently uses a CGM.
Carer of a teenage girl who currently uses a CGM. The people with diabetes and carers were sent tables summarising the identified and filtered technologies and a description of the techniques used and asked to provide comments on specific aspects of each NIGM technology:
1. Do you think the technology would improve your quality of life? And if so, what
issues might it help with?
2. Would you be willing to use this technology? If not, why not?
3. Have you had any personal experience of using this type of technology? If so,
please tell us about your experience.
4. Are you aware of any other non-invasive glucose monitoring technologies that
we have not identified? If so please let us know about them.
Participants were given three weeks to return their comments.
12
4 RESULTS
4.1 IDENTIFICATION AND FILTRATION OF RESULTS
A total of 1,971 technologies were found at the initial identification stage. Searches produced a varying number of relevant technologies depending on the source (Table 1). After the initial filtration, 1,629 were found not to meet the review’s inclusion criteria. Of the remaining 342 technologies, 254 were duplicates and 38 were further excluded as publically available information indicated they were invasive, already available for use or in pre-clinical stages of development (Figure 1). Table 1: Search results by source
Source Number of results
Number of potentially relevant technologies
General 100 33
Published medical literature 113 55
Clinical trial registry & research funding databases
113 14
Horizon Scanning Health technology assessment and research funding databases
237 66
Med-tech specific sources 296 97
Regulatory authorities 65 0
Professional and patient groups 269 26
Specialist journals and conferences 774 50
Developers – diabetes leaders (glucose monitoring)
4 1
Total 1,971 342
Developers were contacted for information on the remaining 50 technologies – 15 responded. Using the information recieved and other publically available information, a further six technologies were excluded due to the technologies no longer being in development. Information on the 44 remaining technologies was sent to the health care professionals and the people with diabetes/carers. The technologies were grouped initially by technology type (continuous NIGM or intermittent NIGM) and further sub grouped by target site, resulting in five tables of technologies. Grouping the technologies allowed comparison between similar technologies within each section. No further technologies were identified by the health professional and people with diabetes. However a further four technologies were excluded based on information that they provided. Thus a total of 40 NIGM technologies met the inclusion criteria and are presented in this review (Appendix 4 and 5). These technologies are referred to by the corresponding number throughout the text.
13
Figure 1: Identification and filtration results.
Search hits (n = 1,971)
Non-relevant hits (n =1,629)
Technologies identified (n =342)
Duplicates removed (n = 254)
Technologies filtered (n = 50)
Technologies further excluded (n = 38)
Technologies excluded (n = 6)
Technologies included in tables for consideration by
clinical experts & people with diabetes (n = 44)
Additional technologies identified
(n = 0)
Technologies included in the final report
(n = 40)
Technologies excluded by clinical experts and people
with diabetes (n = 4)
14
4.2 TYPES OF NIGM TECHNOLOGIES
4.2.1 INTERMITTENT NIGM
There were 24 intermittent NIGM technologies identified. Of these, 12 used the skin as a target site (finger, arm, hand and ear lobe), seven used breath or saliva and five used tear fluid.
4.2.2 CONTINUOUS NIGM
There were 16 continuous NIGM technologies identified. Of these, 13 used the skin as a target site (finger, arm, hand and ear lobe), and three used tear fluid. 4.3 NIGM TECHNIQUES
From the 40 new and emerging NIGM technologies identified (Table 2), three general categories of techniques for measuring glucose levels were identified:
Optical techniques
Transdermal techniques
Electrochemical techniques Table 2: Non-invasive glucose monitoring technique and number of technologies General Technique Specific techniques Number
Optical techniques Absorption spectroscopy 5
Raman spectroscopy 4
Fluorescence 4
Surface plasmon resonance interferometry 2
Optical coherence tomography 1
Photoacoustic spectroscopy 1
Transdermal techniques Impedance spectroscopy 5
Reverse iontophoresis 5
Electrochemical techniques
Enzymatic detection of glucose 7
Amperometry 1
Other Refractive changes in the eye 2
Ultrasonic, electromagnetic and heat capacity
1
Micro sensor and computer technology 1
Unknown 1
40
4.3.1 OPTICAL TECHNIQUES
Optical techniques utilise the different properties of light to interact with glucose in a concentration-dependent manner22. Within this category there were a number of techniques identified that were apparent in the emerging NIGM technologies:
15
Absorption spectroscopy is employed as an analytical chemistry tool to determine the presence of a particular substance in a sample, and, in many cases, to quantify the amount of the substance present21,22.
Technology 13 (breath, intermittent monitor). Relevant types of absorption spectroscopy include:
1. Near-infrared absorption spectroscopy (NIR) which uses a beam of light with a wavelength in the range of 600-2,500nm, which is focused on the body to determine the concentration of glucose within the tissues21,22.
Technology 2 (finger, intermittent).
Technology 8 (finger, intermittent).
2. Mid-infrared absorption spectroscopy (MIR) which uses a beam of light with wavelength in the range of 2,500-10,000nm. It is based on the same principles as NIR but has reduced scattering and increased absorption (high wavelengths)21,22.
Technology 1 (Ball of thumb, index finger, palm below the little finger, ear lobe, intermittent)
Technology 5 (palm, intermittent).
Raman spectroscopy assesses the scattering of single wavelength light. This is dependent on rotational or vibrational energy states within a molecule22.
Technology 6 (finger, intermittent).
Technology 7 (arm or finger, intermittent).
Technology 29 (wrist, continuous).
Technology 36 (finger, continuous). Photoacoustic spectroscopy uses the principle that absorption of light causes ultrasonic waves22. The tissue is illuminated by a light source at a specific wavelength and the absorbed energy results in localised heating22. The small temperature increase results in volumetric expansion which causes an ultrasound pulse to be generated and this can be detected. It is suggested that high tissue glucose concentrations reduce the heat capacity of a tissue and as a result increases the velocity of the generated pulse22.
Technology 10 (ear, intermittent). Optical coherence tomography (OCT) systems use a low-power laser source, an in-depth scanning system, a sampling device and a light detector22. OCT determines the amount of glucose present by assessing the intensity of the reflected/scattered and transmitted light upon interaction with the subcutaneous tissue glucose concentration1.
Technology 24 (eye, intermittent). Fluorescence involves the absorption of light at a high wavelength and the emission of light at a second, less energetic wavelength23.
Technology 4 (finger, intermittent).
Technology 31 (abdomen or upper arm, continuous).
Technology 32 (finger, continuous).
Technology 39 (eye, continuous).
16
Surface plasmon resonance interferometry When particles of light hit a metal surface they cause the electrons within the metal to vibrate. This results in the generation of waves of electrons known as surface plasmons24. The thin metal surface is usually coated with a glucose sensitive ligand and this will bind to glucose molecules detected in the sample of interest. This reaction produces a change in the reflected light which can be measured.
Technology 19 (saliva, intermittent).
Technology 21 (eye, intermittent).
4.3.2 TRANSDERMAL TECHNIQUES
Transdermal techniques involve the measurement of glucose through the skin using either chemicals, electricity or ultrasound. A number of emerging NIGM technologies were found that use a transdermal technique. These can be subdivided into: Reverse iontophoresis This is a transdermal technique that uses the application of physical energy to access the interstitial fluid20,22. A low energy electrical current is applied across the skin by two electrodes that are located next to one another22. The current causes glucose molecules to move across the skin and collect at one of the electrodes20.
Technology 25 (skin, continuous).
Technology 27 (wrist/arm/leg, continuous).
Technology 28 (arm, continuous).
Technology 33 (skin, continuous).
Technology 34 (arm, continuous). Impedance spectroscopy This is also known as dielectric or electrochemical impedance spectroscopy. It measures the dielectric properties of a tissue. A small alternating current is passed across a tissue and the impedance is recorded as a function of frequency. Glucose is indirectly measured by its concentration-dependent interaction with red blood cells22.
Technology 9 (skin between the thumb and forefinger or earlobe, intermittent).
Technology 11 (thumb, intermittent).
Technology 26 (hand, continuous).
Technology 35 (upper arm, continuous).
Technology 37 (wrist, continuous)
4.3.3 ELECTROCHEMICAL TECHNIQUES
This can be subdivided into: Amperometry This is the detection of ions in a solution based on electric current or changes in electric current25.
Technology 38 (eye, continuous).
17
Enzymatic Glucose may be sensed using enzymatic electrodes which catalyse reduction-oxidation reactions. Glucose oxidase (GOx) produces hydrogen peroxide which is directly proportional to the concentration of glucose22.
Technology 14 (saliva, intermittent).
Technology 15 (saliva, intermittent).
Technology 16 (saliva, intermittent).
Technology 17 (saliva, intermittent).
Technology 18 (breath, intermittent).
Technology 22 (tears, intermittent).
Technology 30 (skin, continuous).
4.3.4 OTHER
Other techniques were also identified that didn’t fit into the above three general categories: Micro sensor and computer technology Involves the use of small sensors that are sensitive to glucose26. Readings can be transmitted to a smartphone device.
Technology 40 (tears, continuous). Refractive changes in the eye This measurement is based on polarised light entering the eye and detecting optically active solutes such as glucose which cause the light entering to rotate. The amount the light is rotated by the glucose molecules present can be measured21,23.
Technology 20 (tears, intermittent).
Technology 23 (tears, intermittent) Ultrasonic, electromagnetic and heat capacity Involves the combination of three non-invasive methods (ultrasonic, electromagnetic and thermal).
Technology 12 (ear, intermittent). 4.4 DEVELOPMENT STATUS
Seventeen of the NIGM technologies identified are at the early development stage which ranges from prototype testing to looking for a commercial partner. Twenty-six of the NIGM technologies are currently being developed by commercial companies and 14 by non-commercial developers (research centres and collaborations). Information on timeframe to product launch is limited and only eight of the 40 developers provided details of provisional commercialisation plans. Information on product launch was available in the public domain for two of the technologies. One technology is currently available through the developers’ website (technology 3), two may become commercially available during 2016 (technology 27 & 31), two during 2017 (technologies 1 & 14), three by the beginning of 2018 (technology 35, 36 & 38), one by the beginning of 2019 (technology 20) and one by 2020 (technology 13). One of the technologies received a CE mark approval in April 2014 and is currently being
18
distributed in Europe and Asia but no information on UK launch plans was available (technology 12). No information about timeframe to product launch was available in the public domain for twelve of the technologies identified (technologies 6, 7, 8, 11, 15, 19, 24, 25, 29, 32, 37, 39). 4.5 HEALTHCARE PROFESSIONALS’ PERSPECTIVE
In this section we present a summary of comments made by the healthcare professionals on the NIGM technologies identified. Further comments on the individual technologies can be found in Appendix 4 & Appendix 5
4.5.1 ACCURACY OF THE TECHNOLOGY AND THE TECHNIQUE USED
Most of the healthcare professionals felt unable to comment on the accuracy of the technology and the technique used for measuring glucose levels. This was due to there being “little evidence available” as well as the development stages of most technologies being “too early” to accurately comment. Specific concerns were that the techniques used seemed “too indirect to satisfy the demanding standards which would be required, for instance, by driving regulatory authorities” and that some of the methods used “would be affected by how quickly the glucose changes compared to the capillary”.
A general consensus indicated that fluorescence and spectroscopic techniques may provide the most accurate glucose readings: “I doubt if it will be as robust as or compete with the best of spectroscopic and fluorescent technologies”; “I’m not convinced this technique will survive to completion compared to fluorescence and spectroscopic methodologies”.
4.5.2 TECHNOLOGY INNOVATION
All the healthcare professionals agreed that all of the technologies identified were innovative. Comments included “Not many non-invasive devices currently in development use radiowave spectroscopy” and “It’s innovative because it lasts for so long and is accurate” The ability of a technology to “test for other parameters” or “factor for exercise, diet and BMI” was thought “very exciting”. The specificity of a test was also considered an innovative feature: “This is interesting in that they can use it for lower blood sugar concentrations – I’d want people to be putting dextrose in their mouth at that stage”. Positive comments were also made around the connectivity of the technologies, which included “The ability to transfer wireless data to a smart phone and the cloud and to record other data increases its attractiveness”
4.5.3 TECHNOLOGY IMPACT
Comments around the impact the technology may have on people with diabetes included:
19
“The features of the technology may have a big quality of life impact on patients. It may reduce complications and ambulance call outs” “The reduced financial burden on the NHS in the future could be big if these types of technologies (NIGMs) work” “This is well liked because it’s quick, displays arrows, displays line graph, simple to learn (for patient and healthcare), simple to insert, handset has a long battery life, typically does not need re-charging for 2 weeks, and also has a built in blood glucose meter – so any reading that seems wrong can quickly be checked”
4.5.4 POTENTIAL BARRIERS
Multiple barriers were identified for NIGM technologies coming into routine NHS use. These included “The cost and clumsy kit”, “the size described…make it difficult for day to day use”, “risks of infection”, “reluctance….due to the eyes being involved” and “not prescribed so cannot be used to replace blood glucose monitoring strips for meters”. A comment was made that “trust is a very important issue. If a patient doesn't believe the result in front of them they will quickly discard the whole technology, they generally do not like allowing for lag times, so something that samples slowly, or inaccurately will not be widely accepted”. Similarly it was thought “this methodology seems far too indirect to satisfy the demanding standards which would be required for instance by driving regulatory authorities”.
4.6 PEOPLE WITH DIABETES AND CARERS PERSPECTIVE
In this section we present a summary of comments made by the people with diabetes and their carers on the NIGM technologies identified. Further comments on the individual technologies can be found in Appendix 4 & Appendix 5
4.6.1 TECHNOLOGY INNOVATION AND IMPACT
Most of the comments received indicated that a device to replace fingerprick testing would be welcomed. “If this works and is no bigger in size than current fingerprick meters then I can see this being popular” “This sounds a lot better than having to do fingerprick on my son” “This sounds good if it’s non-invasive and continuous” “Brilliant – I would love this and is much easier for children”
4.6.2 USABILITY AND BARRIERS TO ADOPTION
Overall the people with diabetes and carers liked technologies that were small, discreet, easy to use and had good connectivity. Positive comments included “I like this one - continuous, non-invasive and cloud based”, “…you can see the results in real-time on your phone/watch/tablet and it takes readings every 5-10minutes”, “The size of the patch sounds pleasingly small”, “I like the idea of a watch. It looks neat and many parents and teens are now wearing watches so would be interested in trying this” and that it was “a handheld device”. The people with diabetes and carers also provided comments around possible barriers that may prevent the adoption of a technology.
20
Accuracy There were doubts about “whether fluorescence will be reliable based on individual skin/tissue characteristics”, “the lag between blood and ocular fluid so am not keen on any tear-based technology” and also “a time lag with this fluid (interstitial) so not as accurate a reading as capillary blood which is not great if hypo”.
Safety Issues raised included “the risk of using lasers on my skin over the long term”, “risks with using infrared over a prolonged period of time”, “the idea of a portable laser doesn’t sound very safe” and “the transdermal nature...makes me weary of skin injury” and the lack of information on “alarms for hypos and hypers”.
Ease of use Concerns were raised about “whether you would have to put the gel on your skin every time you need to get a reading. I can’t see my teenager doing that every time”, “keeping a small child still for long enough to do this”, “the idea of having to recharge the watch every 24 hours”, “a 10 minute application process sounding inconvenient”, whether “one child/teen who would allow anyone to insert anything into their eyes” and being “bothered to take it [contact lens] out very night and clean it and reinsert in the morning”.
Discreteness Concerns about the visibility of the product were raised including “this sounds big – I don’t want any more big equipment”, “an earlobe sensor would be continuously on display”, “This doesn’t sound very discreet – I would feel uncomfortable doing this in public [licking a plastic lollipop stick]” and “I wouldn’t wear something on my finger continuously unless it was very discreet”.
Time to results Products that reported slower result times were not popular: “If this was more than 5 seconds, I would say there is little value compared to finger sticks” and “A minute seems a long time to wait for a result”.
21
5 DISCUSSION
In this horizon scanning review, we sought to present an overview of current developments in NIGM technologies. In addition, we explored the perspectives of healthcare professionals and people with diabetes and their carers on emerging technologies identified. In total, we identified 40 NIGM technologies, 39 of which were still being tested in clinical trials and not available for routine use. One technology, (the FreeStyle Libre Flash Glucose Monitoring System, Abbott) can be bought from the developer, the health professionals were aware of its existence and one of the people with diabetes commenting on the technologies had used the device but it is not in routine use in the NHS. From information available at the time of writing this report, it is anticipated that from the remaining 39 technologies, the next NIGM technology currently being tested in clinical trials will appear on the UK market during 2016. Technologies identified fell into one of two groups, intermittent NIGM technologies or continuous NIGM technologies. The intermittent NIGM technologies enabled users to measure glucose levels as and when required and patient activity was needed to perform the test. The continuous NIGM technologies were placed on the target site, such as the arm or wrist, and remained there until further action was needed (such as calibration or charging). These devices provided continuous glucose readings throughout the day/night and some incorporated an alarm which alerted the user if glucose levels became too low or too high. Within these categories the technique used and the target site to measure glucose levels non-invasively differed. Comments on the accuracy of these techniques were limited due to sparse information and many of the technologies being at early stages of development. Comments from people with diabetes and their carers provided a useful insight into the impact NIGM technologies may have on the quality of life of diabetes patients. People with diabetes welcomed the idea of a technology that could monitor glucose levels accurately without the need for finger pricks, eliminating the pain and discomfort associated with this method. It was apparent that for a technology to have the most impact it would need to be continuous, discreet, portable, have the ability to transfer data to a mobile phone and, if intermittent, the time to results would need to be quick. Comments from carers of people with diabetes also reflected the above but the ability for a device to alarm was of particular importance. They commented that when caring for young children who are not hypo aware a device that could provide warning and alarm when intervention was needed would provide benefit over one that didn’t. Carers also state that an intermittent NIGM would need to be easy to use and the non-invasive site accessible - for example technologies using breath and eyes were not considered child and carer-friendly. Healthcare professionals were very interested in a technology that could measure glucose along with other parameters such as Body Mass Index (BMI), exercise and diet. Measurement of other analytes, such as total protein was also considered innovative. However, these were less important to people with diabetes and carers who were mainly interested in glucose measurements only. The accuracy of the technique was, as to be expected, an important aspect of the acceptability of the technology to both the healthcare professionals and people with
22
diabetes and carers. Both expressed concern over the delay that may occur in glucose readings with some of the techniques and the target sites used. Details about the technology design were limited, as many of the technologies are at early stages of development. However, for the technologies where information was available the design and sizes differed. Designs included watches, handheld laser devices and tattoo transfers. Sizes also varied from small patches to a laptop sized device. A summary of desired features from the perspective of healthcare professionals and people with diabetes and carers for future NIGM technologies is provided in Table 3): Table 3: Summary of the desirable features for future NIGM technologies.
Physical properties
Small.
Discrete (i.e. minimally noticeable to others).
Handheld (if an intermittent monitor).
Lightweight.
Wireless.
Compatible with existing pumps and CGMs.
Comfortable to wear (if a continuous monitor).
Appealing to the eye.
Dependability
Safe (including giving warnings and alarms when user intervention is needed).
Reliable (including good battery life).
Accurate.
Functionality
Easy to use.
Usable during exercise, swimming and showering (waterproof).
Overnight use, plus capable of working 24/7 (if continuous).
Doesn’t require calibration.
Clear visual display that is easy to read and understand.
Transmits glucose data rapidly and frequently (to a smartphone).
Quality of life is important in any chronic disease such as diabetes, where the burden of self-management is demanding. Any new development need to add to rather than detract from this. Although, there has been much research into the development of a non-invasive glucose monitoring device1,2,19-23,27 the complexity and accuracy of the measurement process remains a barrier to the development of a truly successful NIGM technology. However, this horizon scanning review indicates that considerable progress has been made in recent years with many technologies in development and some nearing the market. People with diabetes and healthcare professionals will continue to await developments in NIGM technologies with interest.
23
APPENDICES
Appendix 1. Identification sources and search terms
Identification sources Source type Specific sources Website link
General Google http://www.google.co.uk/
Published medical literature
PubMed, Medline & Medline in Progress, & EMBASE
Accessed via http://www.elibrary.bham.ac.uk/
ZETOC – British Library Database
http://www.zetoc.mimas.ac.uk/
The Cochrane Library http://www.cochranelibrary.com/
Clinical trial registries & research funding databases
ClinicalTrials.gov http://www.clinicaltrials.gov/
UKCRN portfolio database http://public.ukcrn.org.uk/search/
WHO International clinical trials registry platform (ICRTP)
http://www.who.int/ictrp/en/
NIHR Evaluation Trials and Studies Project portfolio
http://www.nets.nihr.ac.uk/projects?collection=netscc&meta_P_sand=Project
Horizon Scanning, health technology assessment (HTA), and research funding databases
NIHR BRCs, BRU, CRF, HTC and DEC dataset (2015).
N/A
i4i portfolio of funded projects dataset (Feb 2015)
http://www.nihr.ac.uk/documents/research/CCF%20funded%20research%20data/i4i%20Funded%20Research%20February%202015.xlsx
NIHR HSRIC Database http://www.hsric.nihr.ac.uk/ (database not publically available)
EuroScan International Network
http://euroscan.org/ (limited access to database)
ECRI Institute http://www.ecri.org (subscription required)
AHRQ (Agency for Healthcare Research and Quality) Horizon Scanning System
http://www.effectivehealthcare.ahrq.gov/
CADTH (Canadian Agency for Drugs and Technologies in Health)
http://www.cadth.ca/
Med-tech specific sources
Clinica http://www.clinica.co.uk/
Global Data Medical http://www.globaldata.com/
Medical News Today http://www.medicalnewstoday.com/
MedGadget http://www.medgadget.com/
Fierce Network http://www.fiercemedicaldevices.com/
http://www.fiercediagnostics.com/
Regulatory authorities
MHRA (Medicines and Health products Regulatory Agency)
https://www.gov.uk/government/organisations/medicines-and-healthcare-products-regulatory-agency
FDA Approvals http://www.fda.gov/newsevents/productsapprovals/default.htm
Professional and patient groups
Diabetes UK http://www.diabetes.org.uk/
Diabetes Forecast http://www.diabetesforecast.org/
William Sansum Diabetes Center
http://sansum.org/
American Diabetes Association
http://www.diabetes.org/
24
Advanced Therapies and Technologies in Diabetes (ATTD)
http://www2.kenes.com/
JDRF – Juvenile Diabetes Research Foundation
http://www.jdrf.org.uk/
Diabetes Research in Children (DirecNet) – Jaeb Center for Health Research
http://www.direcnet.jaeb.org/
European Association for the Study of Diabetes (EASD)
http://www.easd.org/
InDependent Diabetes Trust http://www.iddt.org/
INPUT Diabetes http://www.inputdiabetes.org.uk/
Specialist journals and conferences
Diabetes http://diabetes.diabetesjournals.org/
Diabetes Care http://care.diabetesjournals.org/
Clinical Diabetes http://clinical.diabetesjournals.org/
Diabetes Spectrum http://spectrum.diabetesjournals.org/
Journal of Diabetes & Metabolic Disorders
http://www.jdmdonline.com/
Journal of Diabetes Nursing http://www.thejournalofdiabetesnursing.co.uk/
Nutrition and Diabetes http://www.nature.com/nutd/journal/v5/n5/index.html
Journal of Diabetes Science and Technology
http://dst.sagepub.com/
Diabetes UK Professional Conference 2015
https://www.diabetes.org.uk/diabetes-uk-professional-conference/
International Diabetes Federation
http://www.idf.org/calendar
Search terms The technology
Non-invasive glucose monitor; noninvasive glucose monitor
Non-invasive continuous glucose monitor
Home blood glucose monitoring (MeSH term)
Monitoring, home blood glucose (MeSH term)
Blood glucose self-monitoring (MeSH term)
The medical condition
Diabetes Mellitus, Type 1 (MeSH term)
Diabetes Mellitus, Type 2 (MeSH term)
Current phase of research
Clinical, human
Phase I – III
25
Appendix 2. List of developers identified
Commercial developers Company website
DiaMonTech GmbH, Germany http://www.diamontech.de/
OrSense Ltd, Israel http://www.orsense.com/
GlucoSense Diagnostics Ltd, UK http://www.glucosense.net/
Lightouch Medical, Inc., USA http://www.lightouchmedical.com/
LEMM Technologies, LCC., USA www.lemmtechnologies.com MediWise, UK http://www.gluco-wise.com/
Pop Test LLC, USA http://www.diabetespoptest.com/
Eternity Healthcare, USA http://eternityhealthcare.com/
Quick LLLC, USA http://iquickitsalivaanalyzer.com/
Xhale Inc., USA http://xhale.com/
Lein Applied Diagnostics Ltd., UK http://www.lein-ad.com/
Opticology, Inc., USA http://www.opticology.com/
Freedom Meditech, Inc., USA http://www.freedom-meditech.com/
Abbott Diabetes Care, Inc., UK http://www.freestylelibre.co.uk/
Nemaura Medical Inc., UK www.nemauramedical.com
Integrity Applications Ltd., Israel http://www.integrity-app.com/
Guided Therapeutics, Inc., USA http://www.guidedinc.com/
Echo Therapeutics, Inc., USA http://echotx.com/
Biovotion AG, Switzerland http://www.biovotion.com/
DIRAmed LLC, USA http://www.diramed.com/
Calisto Medical, Inc., USA http://www.calistomedical.com/ Noviosense, Netherlands www.noviosense.com
Eyesense GmbH, Germany http://en.eyesense.com/
Novartis Alcon, Switzerland http://www.alcon.com/
Non-commercial developers (research centres and collaborations)
Baylor University, USA
Princeton University, USA
Massachusetts Institute of Technology, USA
Oregon Health & Science University, USA
Islamic Azad University, Iran
Western New England University, USA
University of Newcastle, Australia
Brown University, USA
Mayo Clinic, USA
University of Texas, USA
University of Strathclyde, UK
Bar-Ilan University, Israel.
Imperial College of Science, Technology and Medicine, UK
University of California, San Diego Jacobs School of Engineering, USA
26
Appendix 3. Technical questionnaire sent to developers
About the technology Confidential Y
Name of the technology (+ any other name it is known by)
Commercial developer or funder (if any)
Web link to product page (if any)
Patient group and/or Indication Please include whether type 1 and/or type 2 diabetes and targeted patient groups (including sex, age-range etc).
Brief description of the technology Please include what it is and how it works.
What is the non-invasive technique used e.g. reverse iontophoresis, absorbance spectroscopy, Raman spectroscopy etc?
Where is the target site for the technology e.g. ear lobe, wrist, abdomen?
Sample used (if applicable) e.g. saliva, breath?
Intended use:
Who? E.g. Patient, carer, health professional
Where? E.g. Home use, primary care (GP office), secondary care – hospital?
Usability? E.g. Single-use, disposable, reusable
What is the cost of the technology? Please indicate if there are any other additional costs related to your technology e.g. service and delivery.
Do you have a picture or diagram of the technology? If so, we would be grateful if you could attach a copy and indicate if we have permission to use it in our report. We would acknowledge source.
Stage of development Confidential Y
What phase of clinical research is it at? (e.g. Pre-clinical, Phase 1, Phase 2, Phase 2/3)
Estimated timeframe for CE marking (e.g. Q1/2 2017)
Estimated timeframe for UK/EU launch (e.g. Q1/2 2017)
Is it available in the USA, Canada or Australia?
Research evidence
Please attach papers or provide web links to publications and/or clinical trial registry records
Confidential Y
Published clinical research (including conference abstracts)
Completed but not yet published clinical research
Ongoing clinical trials
27
Appendix 4: New and emerging NIGM technologies identified
Intermittent Glucose Monitors
Table 1: Intermittent Glucose Monitors - Target Site: Skin - Finger, arm, hand, ear lobe. Technology Name and developer Description Technique used Development status
1. Infrared Laser Glucometer. DiaMonTech GmbH, Berlin, Germany. http://www.diamontech.de/
Uses mid-infrared pulses from an infrared laser to excite glucose molecules in the interstitial layer of skin. Absorption of these pulses depends on the concentration of glucose and results in a heat wave migrating to the skin surface, where it is picked up by photo-thermal detection. For use by patients at home with a wearable device planned. Calibration for several users is possible. Indication: Type 1 & 2 diabetes, all ages. Target site: Ball of thumb, index finger, palm below the little finger, ear lobe. The sensor is placed on the skin.
Mid-infrared absorption spectroscopy.
Early clinical development. Mobile prototype for clinical testing – 2016, Home use – 2018 Wearable 2019-2020. Est. CE marking Q2/2017. Est. EU/UK launch Q3 2017.
Comments: Healthcare Professionals This is a novel concept but there is little data available. Spectrometry or ultrasound techniques are also likely to be associated with less potential danger/risk than the use of lasers. Potential Users This sounds like it could be difficult to use and I’m concerned around the use of lasers on my skin long term. How discreet would this be? I wouldn’t be interested if it wasn’t portable. How long would it take to return a result? If this was more than 5 seconds, I would say there is little value compared to fingerpricks. I would use this on my son if it didn’t need calibrating.
28
Technology Name and developer Description Technique used Development status
2. OrSense NBM-200G. OrSense Ltd., Israel. http://www.orsense.com/ http://www.diabetesnet.com/diabetes-technology/meters-monitors/future-meters-monitors/orsense
Detects the near-infrared optical signal of blood that reacts to changes in glucose concentration in blood. Device is portable and claims to be easy to use with results in less than a minute. Also measures haemoglobin and oxygen saturation. Indication: Type 1 & 2 diabetes. Target site: Finger.
Near-infrared absorption spectroscopy.
CE marked but not commercialised. Currently being used for investigation and market awareness purposes only.
Comments: Healthcare Professionals Novel concept but too early to consider its application for use in a clinical setting. Sounds like it is based on infrared technology that we used to use for capillary testing, so likely to be do-able, but may not be totally accurate – I’ve read that this technique was affected by the patient’s hydration. Potential Users If this works and is no bigger than current fingerstick meters, then I can see this being popular. However, a minute seems a long time to wait for a result, most meters now count down from 5 so much quicker.
3. FreeStyle Libre Flash glucose monitoring system Abbott Diabetes Care, Inc., Berkshire, UK. http://www.freestylelibre.co.uk/
Tiny glucose sensor (0.5cm long, about the thickness of a hair) under the skin connected to a water resistant on-body patch (1.5cm diameter), with a wireless touch screen reader device. Sensor remains inserted for 14 days. When the touch screen reader is placed over the sensor patch, it reads the glucose value, shows a glucose trend arrow, and a trend graph for the last eight hours. Provides an Ambulatory Glucose Profile (AGP) by utilizing hypoglycemic and hyperglycemic trends. Indication: Type 1 & 2 diabetes. Target site: Arm.
Unknown.
Can be bought through Abbott Diabetes Care. Current use (if any) in the NHS unknown.
29
Technology Name and developer Description Technique used Development status
Comments: Healthcare Professionals Excellent system currently being used by a number of patients on a self-funding basis within the NHS. However there is no uptake on funding via the NHS. The results appear good and overall feedback from users has been excellent. Has good connectivity and usability of readouts such as line graphs and arrows. It is quick, simple to learn (for patients and healthcare professionals), simple to insert, handset has a long battery life and does not need re-charging for two weeks, and has a built in blood glucose meter so any reading that seems wrong can quickly be checked. Main disadvantage is that it cannot be prescribed so cannot be used to replace blood glucose monitoring strips for meters and also not yet accepted as replacement for blood glucose reading by DVLA in view of the lag between blood and interstitial glucose measurements. It also needs calibrating. Potential Users I have used it and it’s OK. Doesn’t have an automatic alarm and wouldn’t be suitable for people who are hypoglycaemia unaware. I find it accurate, comfortable and user-friendly. It has improved my quality of life. It is useful for measuring glucose levels without having to prick my finger. Trend arrows and graphs provide relevant and useful information. I am very happy with this product. It could be improved by making my pump communicate one-way with the handset, so that a real-time bolus calculator could be created without having to input all my dosage times and amounts manually. This would be a more appealing than making it continuously transmitting.
4. Glucosense. GlucoSense Diagnostics Ltd, London, UK. http://www.glucosense.net/
Based on photonics technology. A small portable laser. When the glass is in contact with the skin, the reflected fluorescence signal varies with the concentration of blood glucose. Will measure, process and display and, in advanced versions, wirelessly transfer data to smart phone or PC. Indication: Type 1 & 2 diabetes. Target site: Finger.
Fluorescence. Ongoing clinical trials and product optimisation required before regulatory approvals and launch.
Comments: Healthcare Professionals An innovative concept. A plausable technology likely to be of interest at least in its continuous monitoring form with ability to connect wirelessly to a smartphone or PC. Potential Users Could be very attractive to a lot of people if it’s small, quick and reliable. Have doubts about whether fluorescence will be reliable based on individual skin/tissue characteristics. The idea of a portable laser doesn’t sound very safe.
30
Technology Name and developer Description Technique used Development status
5. Non-invasive laser device Princeton University, New Jersey USA.
Laser directed target dermal interstitial fluid, which has a strong correlation with blood sugar. Indication: Type 1 & 2 diabetes. Target site: Palm.
Mid-infrared absorption spectroscopy.
In process of implementing field trials. Next stages would involve both hardware and software developments.
Comments: Healthcare Professionals Novel idea but not sure about its use in day to day care as it appears to be in very early stages of development. Potential Users Sounds potentially interesting but not sure if frequent exposure to laser would be safe. An interstitial fluid device and there is a time lag associated with this fluid so not as accurate as capillary blood which is not great if hypo.
6. Non-invasive blood chemistry monitor Lightouch Medical Inc., Pennsylvania, USA. http://www.lightouchmedical.com/services.html
A three minute measurement to obtain both the current blood glucose level and assess whether the blood glucose is rising or falling. Will measure glucose, total protein and other blood and interstitial fluid borne analytes. Indication: Type 1 & 2 diabetes. Target site: Finger.
Raman spectroscopy. No information available.
Comments: Healthcare Professionals Sounds like a novel idea and it is also useful as testing for other parameters. However I’d need to know more about stage of development to comment further. Also have concerns around accuracy of technique as there is a delay in glucose measured in forearm compared to finger. Potential Users Sounds like something that would be useful in a hospital environment rather than at home. Three minutes until a result seems a very long time and I’m not interested in protein and other analyte measurements – just glucose!
31
Technology Name and developer Description Technique used Development status
7. Non-invasive blood glucose monitor. Massachusetts Institute of Technology, USA.
Laptop-sized device using near-infrared light which measures blood glucose levels. Based on DCC (Dynamic Concentration Correction)-Calibrated Raman Spectroscopy Technology. Indication: Type 1 & 2 diabetes. Target site: Arm or finger.
Raman Spectroscopy. No information available.
Comments: Healthcare Professionals Concept is good however size described would make it difficult for day to day use, also appears in very early stages of development. Potential Users Sounds big – I don’t want any more big equipment. I want to use something that is portable and this doesn’t sound convenient to use several times every day.
8. Glycolaser® device Pignolo SpA.
Handheld, mobile phone sized device. Patient rests finger in front of a small window located on the front of the device, which uses a laser light to measure blood glucose. The value is then converted and appears on a small display screen. Indication: Type 1 & 2 diabetes. Target site: Finger.
Near-infrared absorption spectroscopy.
No information available.
Comments: Healthcare Professionals Sounds plausibly practical for one off glucose measurements but no indication whether it might be used for continuous monitoring or trend determination Potential Users I like the sound of this as would give the finger a break from prick testing. I like that it’s a handheld device. This sounds like it would be much easier for children, and would also be good for babies.
32
Technology Name and developer Description Technique used Development status
9. Glucowise™ MediWise, London, UK. http://www.gluco-wise.com/
Measures blood glucose in capillaries using high-frequency radio waves. Includes a wearable sensor and displays the data on smartphone. Integrates a range of measurements including exercise, diet, body mass index, medication and illness and includes cloud-based data management system to store historical Glucowise data. Indication: Type 1 & 2 diabetes. Target site: Skin between the thumb and forefinger or earlobe.
Radiowave spectroscopy.
In development and will be available once clinical trials are completed. The company expect to start taking pre-orders in late 2016.
Comments: Healthcare Professionals Very exciting as it factors for exercise diet and BMI and the ability to transfer wireless data to a smart phone and the cloud and record other data increases its attractiveness. Potential Users Claims to measure/track (exercise/diet/BMI/medication/illness) and would rely on the user entering the data, which is the biggest problem in trying to bring data together. I like the iphone, that it’s continuous and non-invasive. It would be good if it could also connect to an insulin pump. An earlobe sensor would be continuously on display so not very discreet, unless it looked like an earring
10. Analyte measuring device. Oregon Health & Science University, USA.
Handheld device to measure glucose in blood utilizing pressure signals related to otoacoustic emissions or middle ear muscle reflex. Indication: Type 1 & 2 diabetes. Target site: Ear.
Photoacoustic spectroscopy.
Looking for partners.
Comments: Healthcare Professionals Not convinced. We use the ear for temperature, but that is so easy in comparison to blood glucose measurements. Not sure how vascular the middle ear is and think wax might cause problems with reliability especially in children. Potential Users I would not want to put something in my ear to read my glucose.
33
Technology Name and developer Description Technique used Development status
11. Microwave sensor Islamic Azad University
Microstrip that acts as a glucometer. Has a sensor that is a band pass filter (passes frequencies within a certain range and rejects frequencies outside that range). The filter can detect changes in blood glucose levels. Indication: Type 1 & 2 diabetes. Target site: Thumb.
Microwave spectroscopy.
No information available.
Comments: Healthcare Professionals Not sure about its use in day to day care and sounds very early. Potential Users What are the risks of using microwaves? It would give fingers a break and it does sound very useable.
12. GlucoTrack™ Integrity Applications Ltd., Israel. http://www.integrity-app.com/the-glucotrack/
Handheld device to measure blood glucose using an ear clip equipped with sensors and calibration electronics. Uses three techniques - ultrasonic, electromagnetic and heat capacity. Indication: Type 1 & 2 diabetes. Target site: Ear.
Ultrasonic, electromagnetic and heat capacity.
CE mark approval in April 2014. Distributed in Estonia, Turkey, Italy, Lithuania, Latvia, Uruguay, Thailand, Philippine, Spain, Korea, Hong Kong and China. No information on UK launch.
Comments: Healthcare Professionals Appears to be an interesting technology combining three different modalities of measuring glucose which is already operational in parts of Europe. It doesn’t seem to have wireless transmission but appears relatively cheap compared with the one system operational in UK, although doesn’t appear to have the sophistication of readout presentation and interconnectivity. Potential Users This is indiscreet and impractical and I would not want to put this on my ear!
34
Table 2: Intermittent Glucose Monitors - Target Site: Oral – breath and saliva Technology Name and developer Description
Technique used
Development Status
13. Diabetic breathalyzer, New England Breath Technology, Western New England University, USA.
Detects acetone in breath which correlates with blood glucose levels (picture in Appendix 5). Indication: Type 1 and 2 diabetes. Target sample: Breath.
Absorption spectroscopy.
No information available.
Comments: Healthcare Professionals This is a very novel concept and could be used in hospitals. Acetone doesn’t always correlate with blood glucose and this methodology seems far too indirect to satisfy demanding standards required for instance by driving regulatory authorities. This might be useful for measuring ketones, rather than having to do a urine or blood test. Acetone can be high when glucose is high, but not sure how well it correlates with any level of glucose, but I am no expert. Fantastic for ketones though. Diabetic ketoacidosis is life threatening and being able to measure ketones continuously would be so useful and clinically in hospital (A&E and ITU) would be so helpful. Potential Users I think a breath test would be great for quick, non-invasive glucose measurements. I don’t think would be very suitable for a small child.
14. Glucose Pop Test™. Pop Test LLC, USA. http://www.diabetespoptest.com/
Credit card sized, colorimetric device. The patient applies saliva to a bend out lollipop which is bent back. The colour is compared to a standardized colour chart. Single-use and disposable. Point of care test to be used by patients, care giver and/or health professional (picture in Appendix 5). Indication: Type 1 & 2 diabetes. Target sample: Saliva.
Enzymatic detection of glucose in saliva.
CE mark and UK/EU launch 2017. Available in US 2016.
35
Technology Name and developer Description
Technique used
Development Status
Comments: Healthcare Professionals This is a very novel concept and I can see it being potentially exciting for use on near patient testing as long as accuracy is reasonable. This methodology seems far too indirect to satisfy the demanding standards required for instance by driving regulatory authorities. Potential Users This doesn’t sound very discreet – I would feel uncomfortable doing this in public and it could be open to errors in comparing the colours on the stick to the chart.
15. Dual saliva-based sugar monitor. Eternity Healthcare. http://eternityhealthcare.com/eternity-healthcare-to-develop-a-dual-sensor-noninvasive-saliva-based-sugar-monitor-device-to-test-for-diabetes
Utilizes an ultrasensitive sugar monitor and a sensor for salivary amylase enzyme activity. Indication: Type 1 & 2 diabetes. Target sample: Saliva.
Enzymatic detection of glucose in saliva.
No information available.
Comments: Healthcare Professionals This is a very novel concept and I can see it being potentially exciting for use on near patient testing as long as accuracy is reasonable. This methodology seems far too indirect to satisfy the demanding standards required for instance by driving regulatory authorities. Potential Users I don’t think this would be very accurate and is unlikely to be close enough to real-time blood glucose levels to be a reliable method.
36
Technology Name and developer Description
Technique used
Development Status
16. iQuickIt saliva analyser Quick LLC, Connecticut, USA. http://iquickitsalivaanalyzer.com/
Patients insert a stick-sized strip into mouth to collect saliva sample, which is inserted into a hand-held analyser that produces a glucose reading within seconds. Results can be sent to a smart device to be shared, monitored and stored by parents, care-givers and medical professionals. Indication: Type 1 & 2 diabetes. Target sample: Saliva.
Enzymatic detection of glucose in saliva.
Clinical studies underway in America.
Comments: Healthcare Professionals This is a very novel concept and I can see it being potentially exciting for use on near patient testing as long as accuracy is reasonable. I’m not convinced salivary glucose techniques will survive competition from fluorescence and spectroscopic methodologies. Potential Users I would not want to do this in public and doesn’t sound like it would be accurate. I really like this – if the accuracy is good and the reading appears on the device then I would consider using it on my son.
17. Glucose sensor University of Newcastle, Australia. http://newcastleinnovation.com.au/partnership-opportunities/non-invasive-glucose-monitoring
Glucose sensors that integrate glucose oxidase enzyme into a film claimed to be capable of sensing blood sugar concentrations 100 times lower than commercially available glucose sensors. Indication: Type 1 & 2 diabetes. Target sample: Saliva.
Enzymatic detection of glucose in saliva.
Currently at proof-of-concept stage.
37
Technology Name and developer Description
Technique used
Development Status
Comments: Healthcare Professionals This is a very novel concept and I can see it being potentially exciting for use on near patient testing as long as accuracy is reasonable. I’m not convinced salivary glucose techniques will survive competition from fluorescence and spectroscopic methodologies. This is interesting in that they can use it for lower blood sugar concentration. Potential Users I don’t like the idea of putting something in my mouth to find out what my glucose levels are, and it doesn’t sound like it would be accurate. I really like this and would use it on my son if it is as accurate as they claim.
18. Breath-based blood glucose monitor Xhale, Inc., Florida, USA. http://xhale.com/
Measures glucose in exhaled breath condensate. The user blows into the device, and obtains a read-out of blood glucose level. Indication: Type 1 & 2 diabetes. Target site: Breath.
Enzymatic detection of glucose in breath.
The company is looking for partners to further develop this technology.
Comments: Healthcare Professionals This is a very novel concept but seems very early and as with the salivary technologies I doubt if it will be as robust or compete with the best of spectroscopic and fluorescent technologies. This is interesting in that they can use it for lower blood sugar concentration. Potential Users I think a breath test would be great for quick, non-invasive glucose measurements but I foresee too many potential contaminants to have confidence in this method.
19. Saliva monitor Brown University, Rhode Island, USA.
Uses a sensor that relies on plasmonic interferometry, a light-based way of detecting chemical compounds, and a dual-enzyme assay that works as a dye to mark glucose. Indication: Type 1 & 2 diabetes. Target sample: Saliva.
Plasmonic interferometry.
No information available.
38
Technology Name and developer Description
Technique used
Development Status
Comments: Healthcare Professionals Very novel concept but seems very early and as with the salivary technologies I doubt if it will be as robust or compete with the best of spectroscopic and fluorescent technologies. This is interesting in that they can use it for lower blood sugar concentration. Potential Users It’s hard to imagine how this device would look and feel from the information provided and I am very sceptical about this method of analysing glucose. I foresee too many potential contaminants to have confidence in this method. Further, saliva-based measurement is unlikely to be close enough to real-time blood glucose levels to be a reliable method.
Table 3: Intermittent Glucose Monitors - Target Site: Eye – tears
Technology Name and developer Description Technique used
Development Status
20. One Look Lein Applied Diagnostics Ltd., Reading, UK. http://www.lein-ad.com/diabetes_care.html
Mobile phone sized device that the user holds up to their eye and looks into to obtain a reading. The meter measures refractive changes in the anterior chamber of the eye that are related to changes in glucose levels. Reusable meter (see picture in Appendix 5). Indication: Type 1 & 2 diabetes, gestational, both genders, all ages. Target site: Eye.
Refractive changes in anterior chamber of eye that are related to changes in glucose levels.
CE mark Q4 2018. UK launch Q1 2019.
39
Comments: Healthcare Professionals An interesting concept however I can see some reluctance for use in patients due to the eyes being involved. I doubt if it will be as robust or compete with the best of spectroscopic and fluorescence technologies. This would be affected by how quickly the glucose changes in the tears compared to the capillary. We need to know the absolute value of the circulating glucose is not what it was even 5 minutes ago. However, a guide is always useful just like the CGMs that we have now, so it’s not as much of a no as the saliva – and could be used while people try to recover their lows. Potential Users I have concerns about the lag between blood and ocular fluid so I am not keen on any tear-based technology and I also wonder if dehydration would affect the accuracy of the reading. It is interesting though. I’m not sure I could keep a small child still for long enough to do this.
21. Ocular Tear Glucose Pen. Glucopen, Ocular Glucose Monitor. Tear Glucose Research, LLC. Opticology, Inc. www.opticology.com
The small tip of a pen sized instrument touches the tear meniscus providing episodic measurements of ocular glucose. Laser light interrogates a thin film of metal which has bound glucose sensitive chemistry (ligand). This chemistry binds with glucose (analyte) in the tears and produces a change in the reflected laser light. The pen is single-use and comes with disposable sensor tips. It is intended to be used by patients at home (see picture in Appendix 5). Indication: Type 2 diabetes. Target site: Eye.
Surface plasmon resonance.
Early clinical development. Has been used in informal studies for measuring constituents of the tear film. A study on tear glucose should be completed by Q4/2015. No further update available.
Comments: Healthcare Professionals An interesting concept however I can see some reluctance for use in patients due to the eyes being involved. I doubt if it will be as robust or compete with the best of spectroscopic and fluorescence technologies. Potential Users I have serious concerns about the lag between blood and ocular fluid so I am not keen on any tear-based technology. I also wouldn’t want anything this close to my eye and how would I perform a measurement on a moving bus or train? This does sound interesting but not great for contact lens wearers and I can’t imagine this is child friendly.
40
22. TOUCH tears glucose, tear glucose biosensor. Mayo Clinic, Arizona, USA. http://labellelab.asu.edu/2011/03/17/diabetes-self-monitoring-shed-a-tear-to-test-blood-sugar-level/
This electrochemical based device uses GDH-FAD (glucose dehydrogenase-FAD dependent) enzyme. Captures basal tears and measures the tear fluid glucose levels without stimulating a glucose/stress response. It is intended to be used by patients, carers and health professionals (see picture in Appendix 5). Indication: Type 1 & 2 diabetes, all ages. Target site: Eye – tears.
Enzymatic detection of glucose.
Early clinical development. Clinical trials to be conducted at Mayo Clinic. The project team will seek additional support from the National Institutes of Health and industry to fund the trials.
Comments: Healthcare Professionals An interesting concept however I can see some reluctance for use in patients due to the eyes being involved. I’m not convinced by this technology and it misses out on the connectivity which comes with some of the fluoroscopic and spectroscopic devices. Potential Users I have serious concerns about the lag between blood and ocular fluid so I am not keen on any tear-based technology. I also wouldn’t want anything this close to my eye and how would I perform a measurement on a moving bus or train? This does sound interesting but not great for contact lens wearers and I can’t imagine this is child friendly.
23. I-SugarX Freedom Meditech, Inc., California, USA.
Takes direct measurement of glucose in aqueous humour of the eye. Indication: Type 1 & 2 diabetes. Target site: Eye.
Refractive changes in the anterior chamber of the eye.
Human clinical trials were planned to commence in 2012 – no further update available.
http://labellelab.asu.edu/2011/03/17/diabetes-self-monitoring-shed-a-tear-to-test-blood-sugar-level/
http://labellelab.asu.edu/2011/03/17/diabetes-self-monitoring-shed-a-tear-to-test-blood-sugar-level/
41
Comments: Healthcare Professionals An interesting concept however I can see some reluctance for use in patients due to the eyes being involved. It is also another indirect technique and I have my reservations on its accuracy. Potential Users I have serious concerns about the lag between blood and ocular fluid so I am not keen on any tear-based technology. I also wouldn’t want anything this close to my eye and how would I perform a measurement on a moving bus or train? This does sound interesting but not great for contact lens wearers and I can’t imagine this is child friendly.
24. Optical Coherence Tomography University of Texas, USA.
An optical tomography system which determines glucose levels by assessing intensity of reflected/scattered and transmitted light upon interaction with subcutaneous tissue glucose concentration. Indication: Type 1 & 2 diabetes. Target site: Eye.
Optical coherence tomography.
No information available.
Comments: Healthcare Professionals An interesting concept however I can see some reluctance for use in patients due to the eyes being involved. It is also another indirect technique and I have my reservations on its accuracy. Retinal tomography is already being used to understand more about diabetes eye disease, so this might be a technology worth investigating and if it is looking at the subcutaneous tissue in the eye then that is through the arteries so would give a very precise measurement. Potential Users I have serious concerns about the lag between blood and ocular fluid. I like this if you only have to look into a machine rather than having something touch your eye.
42
Continuous Glucose Monitors
Table 4: Continuous Glucose Monitors - Target site: Skin – finger, arm, hand and ear.
Technology Name and developer Description
Technique used
Development Status
25. Non-invasive blood glucose monitor LEMM Technologies, LLC.
A portable, programmable, reverse iontophoresis (RI) based skin electrode/biosensor system which extracts glucose and lactate using a gel electrode. It measures or/detects intermittently or continuously glucose or lactate. Indication: Type 1 & 2 diabetes. Target site: Skin (exact site unknown).
Reverse iontophoresis. No information available.
Comments: Healthcare Professionals This is a novel idea and concept but there are no details of where the testing would be done and at what stage of development it is in. A glucose monitoring watch type device was developed some years ago but fell by the wayside because of problems related to inaccuracy when a patient sweated heavily. These devices can be affected by perspiration and climate – it makes them less reliable. They may have overcome that problem, but people who are about to become hypoglycaemic sweat due to the effect of the low glucose on the autonomic nervous system. Potential Users I only want to know about my glucose and I would have concerns whether you would have to put the gel on your skin every time you need to get a reading. I can’t see my teenager doing that every time. This sounds good if it’s non-invasive and continuous. The problem with a CGM and a small child is continually finding sites to move the cannula around as there aren’t a lot of areas especially when dealing with a CGM cannula and a separate pump cannula site.
26. Ultra wide-band pulse dispersion spectrometry. Baylor University, Texas, USA.
Sends low level radiofrequency/microwave signals into patient’s tissue. Portable and reusable. For use by patients, initially as an alarm device; later as a glucometer for insulin dosing. Indication: Type 1 & 2 diabetes, all ages. Target site: Hand; other application sites are being developed.
Radiowave spectroscopy.
Early concept demonstration.
43
Technology Name and developer Description
Technique used
Development Status
Comments: Healthcare Professionals Innovative technology, not many devices use radiowave spectroscopy. Could possibly monitor glucose levels accurately. The features of the technology are significantly innovative and may have a big quality of life impact on patients. It may reduce complications and ambulance call outs. The reduced financial burden on the NHS in the future could be big if these types of technologies (NIGMs) work. The potential barriers with this technology maybe the cost and ‘clumsy’ kit. Using something that can test the trend that the blood glucose is going in would be useful, but in the long run it needs to give absolute numbers. Potential Users This could be useful if it were indicated to replace fingersticks for insulin dosing but I have concerns about the risk of using microwave signals on my skin over the long term.
27. sugarBEAT™ system Nemaura Medical Inc., Loughborough, UK. www.nemauramedical.com
Disposable sensor-patch (1.5cm x 1.5cm) is applied to skin and connected to a laptop-like device. It painlessly extracts interstitial fluid from beneath the skin into the sensor-patch. The patch requires a two hour warm up period, during which it equilibrates with the skin. After this it is designed to work continuously for at
least twelve hours. The device detects and records glucose levels within the patch up to four times per hour. Glucose levels can be seen on a display screen on the device, with additional alarms to alert the user to very high or rapidly falling glucose levels. Single use, disposable patches (see picture in Appendix 5). Indication: Type 1 & 2 diabetes and pre-diabetic glucose monitoring. Target site: Wrist/arm, leg.
Reverse iontophoresis.
Estimated CE mark 2016. Estimated EU/UK launch 2016. The company anticipates launching in Europe and parts of the Middle East and Hong Kong in 2016.
44
Technology Name and developer Description
Technique used
Development Status
Comments: Healthcare Professionals It’s a novel concept however if the patients or carers have to change it every 12 hours I can see some reluctance in its uptake. If it is robust-they will need to demonstrate that they have overcome the problems associated with excessive sweating. Potential Users I don’t like the idea of having to recharge the watch every 24 hours. Could this be worn underwater? Four readings per hour does not sound great – my son’s levels can change dramatically in that time. I don’t like the sound of the 2-hour warm up period and it only lasting for 12 hours. It doesn’t sound very practical.
28. Transdermal continuous glucose monitoring technology University of Strathclyde, Glasgow, UK.
Extracts glucose using a sensor on the skin, connected to a hand-held analyser which continuously monitors glucose. Single use and disposable. Indication: Type 1 and type 2 diabetics who test blood glucose daily. Target site: Various sites but arm used most routinely to date.
Reverse iontophoresis.
CE marking and UK launch, investor dependent. Initial funding from EPSRC, subsequent funding by Scottish Enterprise’s Proof of Concept Fund. Subsequent TSB/Innovate UK funding with industry partners Healthy volunteer study and small clinical study in a diabetic population has completed.
45
Technology Name and developer Description
Technique used
Development Status
Comments: Healthcare Professionals A good concept and I would be interested in seeing the data and its accuracy before considering its use. This has potential only if it can be demonstrated that it has overcome the problems alluded to excessive sweating. I suspect the iontophoresis technologies might have a cost advantage over the fluoroscopic and spectroscopic technologies but first it must be shown to be robust. Potential Users The transdermal nature of this device makes me weary of skin injury. I like the idea of this but would require alarms. How is the fluid ‘extracted’? Is this information uploaded to the cloud for use on tablets and smart phones?
29. Biometric glucose system Bar-Ilan University, Israel.
A watch-like sensor with a laser that illuminates a patch of skin on the wrist near an artery, and a camera that measures changes over time in the light that is back scattered off the skin. Indication: Type 1 & 2 diabetes. Target site: Wrist.
Raman spectroscopy.
In 2014 the company anticipated that a commercial version of the device would reach the market within two to three years. No further update available.
Comments: Healthcare Professionals More information is needed about the stage of development to comment its impact. Potential Users This sounds OK but not very practical and not so suitable for a child. What about exercise and swimming? I would need a device that can be used at all times during all activities.
46
Technology Name and developer Description
Technique used
Development Status
30. Symphony® Echo Therapeutics, Inc. http://echotx.com/
A patch sensor is applied to an area of skin that is exfoliated using a pen-like device. The glucose sensor continuously measures glucose utilises glucose oxidase enzyme technology. A proprietary algorithm converts data to accurate glucose values that are wirelessly transmitted. Results can be displayed on a mobile platform or cloud service. Indication: Type 1 & 2 diabetes. Target site: Skin.
Glucose oxidase enzyme technology.
Developing commercial partnerships for marketing and distribution in discussion.
Comments: Healthcare Professionals This sounds an exciting concept but at very early stage of development. It potentially could be a very interesting technology because of the good connectivity planned for device and possibly better affordability. This sounds like a possibility if it is not affected by heat, cold and sweat and abrasion is not too severe, but probably relies on the right amount of exudates from the skin so may well be affected by heat cold and sweat. Potential Users The requirement to exfoliate the skin makes me nervous about the potential for irritation and how often would you need to change the sites? I like this one – continuous, non-invasive, cloud based and you can see the results in real-time along with taking readings every 5-10 minutes. It would be useful if it talked to the insulin pump.
31. EyeSense fibre optic sensor EyeSense GmbH, Germany. http://en.eyesense.com/product/fibersense-technology-continuous-glucose-monitoring/product-information/
Continuous fibre optic sensor with built in alarms for hyper and hypoglycaemia. Indication: Type 1 & 2 diabetes. Target site: Abdomen or upper arm.
Fluorescence. The company anticipates the market launch of the fibre optic sensor will likely be in 2016.
47
Technology Name and developer Description
Technique used
Development Status
Comments: Healthcare Professionals A Good concept especially with built in alarm systems as well. I can see it being useful in Type 1 DM. This sounds good. Eye’s need to be open for all of the retinal ones, so perhaps worth a thought that they won’t be so practical for low glucose levels at night. Potential Users I like the sound of this one as it has alarms and it’s continuous. I’m not too sure about this one, it appears to be the same as Dexcom and it looks rather large and sounds invasive.
32. Glucosense CGM GlucoSense Diagnostics Ltd, London, UK. http://www.glucosense.net/
Low-powered laser sensor head collects and measures data, and may be connected to a smart phone or PC to send alerts to the user when needed. Indication: Type 1 & 2 diabetes. Target site: Finger.
Fluorescence. No information available (see Technology 4 for intermittent monitor).
Comments: Healthcare Professionals An interesting concept but no information about stage of development. A plausible technology likely to be of interest at least in its continuous monitoring form with the ability to connect wirelessly to a smartphone or PC. Potential Users I wouldn’t wear something on my finger continuously unless it was very discreet, and the use of lasers in concerning. Talking to the phone is good.
33. Microprobe Array Continuous glucose monitor Imperial College of Science, Technology and Medicine. London, UK.
A wearable patch (~1 cm2), containing microscopic projections (microprobes) that penetrate the outermost skin layer. It accesses interstitial fluid to sense its glucose content without stimulating skin nerve fibres or reaching blood vessels within skin layers. The microprobe surface has the consistency of sandpaper. It is pushed into the skin with an applicator to penetrate through the skin layers and access the interstitial fluid. The device is disposable. Indication: Type 1 & 2 diabetes. Target site: Skin (exact site unknown).
Reverse iontophoresis. The company aim to further develop the device through clinical studies in non-diabetic subjects and subjects with T1DM. NIHR i4i funded project.
48
Technology Name and developer Description
Technique used
Development Status
Comments: Healthcare Professionals A really interesting concept and I note the liaison with NIHR which should lead to good quality data on accuracy. Being a patch hopefully it won’t be affected by heat cold and sweat. Potential Users This sounds interesting, especially if it is sturdy enough to withstand routine bathing, skin bending/stretching and contact with clothing (rubbing). Would this hurt? I like the sound of it if not. I would be interesting I knowing how often would you have to change it and whether or not it would talk to a smart phone. What about alarms? This sounds quite painful! The size of the patch sounds pleasingly small and I would be willing to try this.
34. Temporary tattoo UCSan Diego Jacobs School of Engineering, California, USA. http://www.jacobsschool.ucsd.edu/news/news_releases/release.sfe?id=1691
Carefully patterned electrodes printed on temporary tattoo paper. A mild electrical current applied to the skin for 10 minutes forces sodium ions in the fluid between skin cells to migrate toward the tattoo’s electrodes. These ions carry glucose molecules that are also found in the fluid. A sensor built into the tattoo then measures the strength of the electrical charge produced by the glucose to determine glucose levels. Indication: Type 1 & 2 diabetes. Target site: Arm.
Reverse iontophoresis. Very early – at the moment the tattoo doesn’t provide the numerical readout that a patient would need to monitor his or her own glucose.
Comments: Healthcare Professionals I’m not sure about this being able to apply to common use. A Tattoo insinuates puncturing the skin, so maybe it might be OK, but admits to needing calibration, so the patient will still need to use a lancet. Potential Users This sounds interesting, especially if it is sturdy enough to withstand routine bathing, skin bending/stretching and contact with clothing (rubbing). However, a 10 minute application process sounds inconvenient. My son would love a tattoo – this would not be a hard sell to get him to wear it! This would also appeal to the majority of teens and young people.
49
Technology Name and developer Description
Technique used
Development Status
35. Vital Sign Monitor 3 Biovotion AG, Zurich, Switzerland. http://www.biovotion.com/
Designed to continuously monitor blood glucose levels using a multi-sensor technology approach (see picture in Appendix 5). Indication: Type 1 & 2 diabetes. Target site: Upper arm.
A combination between dielectric, impedance and optical spectroscopy
Phase 2/3 clinical trials. Estimated CE mark Q2 2017. Estimated EU/UK Q1 2018.
Comments: Healthcare Professionals A novel concept but at a very early stage of development. Potential Users This sounds good and I like the idea of a watch. It looks neat and many parents and teens are now wearing watches so would be interested in trying this. It looks too big to be worn discreetly and conveniently.
36. Critical care glucose monitor DIRAmed, LLC., Ohio, USA. http://www.diramed.com/diramed_technology.html
Transmits infrared light into skin. It is based on Raman spectroscopy. Sensors detect changes in properties of the light as a result of interactions with analytes in the body. The company intend on developing it for home and hospital use. Indication: Type 1 & 2 diabetes. Target site: Finger.
Raman spectrometry. The company intend on developing their glucose meters by 2018.
Comments: Healthcare Professionals Potentially a reliable technology but insufficient detail available to comment. Potential Users This sounds better than constantly finger pricking. A similar device that was in development found that raman spectroscopy suffered from light scattering, meaning a large dark patch of fabric would be needed to shield the test area from scattered light. I doubt this will be any different.
50
Technology Name and developer Description
Technique used
Development Status
37. Glucoband® Calisto Medical, Inc.,
A wrist-watch like device with fully integrated LCD screen, electronic circuits, integrated electrodes, battery and adjustable wrist-band which utilizes impedance spectroscopy. The initial measurement process takes only a few minutes, however, in the monitoring mode, measurements can be continuous and only the frequency of measurements must be determined. Glucoband® targets diabetics, who are measuring their own blood glucose, and medical personnel who are using blood glucose measuring and monitoring devices in clinics, hospitals and other point-of-care facilities. Indication: Type 1 & 2 diabetes. Target site: Wrist.
Impendence spectroscopy.
No information available.
Comments: Healthcare Professionals A good idea however no information about stage of development and this could be affected by sweat when a patient is hypoglycaemic. Potential Users I don’t think my son would wear this – it sounds more suitable for adults. I like the idea of a watch and great if the measurements are continuous and I would also want it to alarm.
51
Table 5: Continuous Glucose Monitors - Target site: Eyes – tears.
Technology Name and developer Description
Technique used
Development Status
38. Noviosense glucose sensor Noviosense, Netherlands. www.noviosense.com
The device consists of a 15mm-long, metal coil that is coated in a hydrophilic gel, which the patient places into the lower eyelid. The coil moves to the correct place in the eye and the gel coating hydrates and swells creating a contact between the metal coil and the fluid in the eye. A smart phone app measures the glucose levels. The device is disposable (see picture in Appendix 5). Indication: Type 1 & 2 diabetes, all ages. Target site: Eye.
Amperometry.
NovioSense is currently actively seeking both strategic partners and risk capital to accelerate the development of the technology to clinical validation and market entry. They expect to begin market introduction Q1 2018.
Comments: Healthcare Professionals I can’t see it being commonly used due to the use of the eyes and risks of infection. I think this sound like a bad idea. In a similar way to inhaled insulin – I wouldn’t want to put something in my lungs?? this is eyes!! that may cause harm when a needle works very well for 99.9% of people. Finger lancing would be preferable to anything being invasive into the eye. Potential Users I would not put this in my eye – sounds scary! My son would not allow me to put this in his eye. I cannot think of one child/teen who would allow anyone to insert anything into their eyes. I looked at the photos and absolutely could not have that anywhere near my eyes let alone inserted into the lower lid. An awful idea! I would not consider using this. I can't imagine wearing a 15mm coil and it being comfortable.
52
Technology Name and developer Description
Technique used
Development Status
39. EyeSense eye sensor EyeSense GmbH, Germany. http://en.eyesense.com/product/eyesense-technology-precise-glucose-monitoring-at-the-eye/product-information/
Inserted under the conjunctiva and continuously measures blood glucose levels. It reacts reversibly to the glucose concentration and correspondingly emits fluorescence intensity, correlated to the glucose concentration. The implantation is painless and takes only three minutes. The sensor is not visible and can be worn for up to one year before being replaced. In this time, a small monitoring hand device is used for monitoring. Its emitted light falls on the eye sensor and reads out the returned optical signal sent from the sensor. Once the device is calibrated the results are expressed in the usual blood glucose measuring units. Indication: Type 1 & 2 diabetes. Target site: Eye.
Fluorescence. The eye sensor will be launched after the fibre optic sensor (technology number 35).
Comments: Healthcare Professionals I can’t see it being commonly used due to the use of the eyes and risks of infection. Potential Users I wouldn’t put this in my eye; what happens if it malfunctions? I’m not sure about this one. A 3 minute insertion that needs to be performed by a healthcare professional makes this an expensive and inconvenient option, but if the sensor lasts for a year, that might make up for it. I don't like the idea of a sensor inserted under the conjunctiva, though, and would be concerned about infection risk and irritation. It sounds like the handheld device needs to emit light which is picked up by the sensor, so I can't imagine how this could be a continuous glucose monitor.
40. Smart lens Novartis Alcon, Surrey, UK and Google[x] – team within Google Ltd., London, UK.
Non-invasive sensors, microchips and other miniaturised electronics are embedded within contact lenses. Designed to measure tear fluid in the eye and connects wirelessly with a mobile device (see picture in Appendix 5). Indication: Type 1 & 2 diabetes. Target site: Eye.
Micro sensor and computer technology.
Early stage development.
53
Technology Name and developer Description
Technique used
Development Status
Comments: Healthcare Professionals I can’t see it being commonly used due to the use of the eyes and risks of infection. This sounds better as it states non-invasive and is working on tear fluid. However, if it stays in the eye it is a risk of irritation and infection. Potential Users The potential cost/benefit ratio of this proposal is not positive. We’d also face the issues around people with diabetes who want to wear regular contact lenses not being able to take up this technology, unless there is some magic way of doing 2 lenses or making the glucose sensing lens also corrective. As an adult that wears contact lenses, if this was prescription strength too and the thickness of a daily disposable contact lens not an uncomfortable monthly lens I would be interested. However, I’m not sure I could be bothered to take it out very night and clean it and reinsert in the morning, would prefer continuous device 24 hours without the daily maintenance. This is different! Many millions wear contact lenses, does it alarm for hypers and hypos? I have tried contact lenses and couldn't get on with them as my eyes are too dry. This may be a problem for many people with long standing diabetes. This option would preclude anyone who wore corrective contact lenses.
54
Appendix 5: Pictures of NIGM technologies
All pictures are presented with the permission of the named developer Technology
number Technology name
and developer Picture
13 Diabetic breathalyzer, New England Breath
Technology.
14 Glucose Pop Test™. Pop Test LLC, USA.
20 One Look
Lein Applied Diagnostics Ltd
21 Ocular Tear Glucose
Pen. Glucopen, Ocular Glucose
Monitor. Tear Glucose
Research, LLC. Opticology, Inc.
55
22 TOUCH tears glucose, tear glucose
biosensor. Mayo Clinic, Arizona,
USA.
27 sugarBEAT™ system
Nemaura Medical Inc., Loughborough,
UK.
35 Vital Sign Monitor 3
Biovotion AG, Zurich, Switzerland.
38 Noviosense glucose
sensor Noviosense, Netherlands.
40 Smart lens
Novartis Alcon, Surrey, UK and
Google[x] – team within Google Ltd.,
London, UK.
56
REFERENCES
1 Vaddiraju S, Burgess DJ, Tomazos I et al. Technologies for continuous glucose monitoring: current
problems and future promises. Journal of Diabetes Science and Technology 2010:4(6);1540-1562. 2 Zhang W, Du Y, Wang ML. Noninvasive glucose monitoring using saliva nano-biosensor. Sensing
and Bio-Sensing Research 2015:4;23-29. 3 Livestrong.com. The importance of glucose. http://www.livestrong.com/article/133891-the-
importance-glucose/ Accessed 2 February 2016. 4 Diabetes UK. What is diabetes? https://www.diabetes.org.uk/Guide-to-diabetes/What-is-diabetes/
Accessed 2 February 2016. 5 JDRF. What is type 1 diabetes? https://jdrf.org.uk/about-type-1-diabetes/understanding/what-is-type-
1-diabetes/ Accessed 24 November 2015. 6 Diabetes UK. What is type 2 diabetes? https://www.diabetes.org.uk/Guide-to-diabetes/What-is-
diabetes/What-is-Type-2-Diabetes/ Accessed 24 November 2015. 7 Diabetes UK. Diabetes: Facts and Stats version 4. Revised November 2015.
https://www.diabetes.org.uk/Documents/Position%20statements/Diabetes%20UK%20Facts%20and%20Stats_Dec%202015.pdf
8 Diabetes UK. Diabtest prevalence 2014 (June 2015). https://www.diabetes.org.uk/About_us/What-we-say/Statistics/Diabetes-prevalence-2014/ Accessed 29 February 2016
9 National Institute of Health and Care Excellence. Type 1 diabetes in adults: diagnosis and management. NICE guidelines NG17. London; NICE: Published August 2015.
10 Diabetes UK. Hypos and Hypers. https://www.diabetes.org.uk/Guide-to-diabetes/Complications/Hypos-Hypers/ Accessed 2 February 2016.
11 NHS Choices. Diabetic ketoacidosis. http://www.nhs.uk/Conditions/diabetic-ketoacidosis/Pages/introduction.aspx Accessed 2 February 2016.
12 Benjamin EM. Self-monitoring of blood glucose: the basics. Clinical Diabetes 2002:20(1);45-47. 13 Diabetes UK. Position statement. Self-monitoring of blood glucose levels for adults with type 2
diabetes. April 2013 https://www.diabetes.org.uk/Documents/Position%20statements/Diabetes-UK-position-statement-SMBG-Type2-0413.pdf
14 National Institute of Health and Care Excellence. Diabetes (type 1 and 2) in children and young people: diagnosis and management. NICE guidelines NG18. London; NICE: Published August 2015.
15 National Institute of Health and Care Excellence. Type 2 diabetes in adults: management. NICE guidelines NG28. London; NICE: Published December 2015.
16 Diabetes UK. Testing. https://www.diabetes.org.uk/Guide-to-diabetes/Monitoring/Testing/ Accessed 8 December 2015.
17 Diabetes.co.uk. Blood glucose meter guide. http://www.diabetes.co.uk/diabetes_care/blood_glucose_monitor_guide.html Accessed 8 December 2016.
18 Diabetes.co.uk Continuous glucose monitoring. http://www.diabetes.co.uk/cgm/continuous-glucose-
monitoring.html Accessed 16 March 2016 19 Klonoff DC. Continuous glucose monitoring. Diabetes Care 2005:5(28);1231-1239. 20 Eduardo Ferrante de Amaral C and Wolf B. Current development in non-invasive glucose monitoring.
Medical Engineering & Physics 2008;30:541-549. 21 Vashist SK. Non-invasive glucose monitoring technology in diabetes management: A review.
Analytica Chimica Acta 2012;750:16-27. 22 Oliver NS, Toumazou C, Cass AEG et al. Glucose sensors: a review of current and emerging
technology. Diabetic Medicine 2009;29:197-210. 23 Smith J. The Pursuit of noninvasive glucose: “Hunting the deceitful turkey”. Fourth edition: Revised
and expanded 2015. 24 IEEE Spectrum. Cheap Plasmonic Interferometer could enable prickles glucose monitor.
http://spectrum.ieee.org/nanoclast/biomedical/devices/cheap-plasmonic-intererometer-could-enable-prickless-glucose-monitor Accessed 16 March 2016.
25 Roussel TJ, Jackson DJ, Baldwin RP et al (2008). Encyclopedia of Microfluidics and Nanofluidics. USA: Springer. 39-47.
26 Healthline.com. Google Scientists Create Contact Lens to Measure Blood Sugar Levels in Tears http://www.healthline.com/health-news/diabetes-google-develops-glucose-monitoring-contact-lens-012314#3 January 2014
27 Larin KV, Motamedi M, Eledrisi M et al. Noninvasive blood glucose monitoring with optical coherence tomography. Emerging Treatment and Technology, Diabetes Care 2002;25(1):2263-2267.
Related Documents
